Hereditary hemochromatosis is a disorder of iron metabolism that leads to iron overload and can progress to fatal complications such as terminal hepatic failure, primary hepatocellular carcinoma, and congestive heart failure. Gene mutations have been identified that are associated with hemochromatosis, although many individuals with these mutations do not display signs of hemochromatosis. Therefore, it is important to determine factors interacting with these genes that are associated with hemochromatosis outcomes. Telomere length is a novel biomarker that represents biological aging. It is unclear how hemochromatosis genes and iron overload relates to telomere length. The aims of the study are to 1) Determine the relationship between leukocyte telomere length and hemochromatosis related outcomes, 2) Examine the relationship between telomere length and genotype and phenotype indicators for hemochromatosis, and 3) Analyze the impact of lifestyle and clinical care on telomere length and hemochromatosis outcomes. We propose to conduct an analysis of the Hemochromatosis and Iron Overload Screening (HEIRS) Study public use data set. We will conduct new analyses of telomere length from stored samples and merge that with other existing data from this study. During this two-year project, we will examine the impact of treatment and lifestyle variables on telomere length and hemochromatosis related outcomes among these individuals to see which variables act as buffers to aging and morbidity risk. We will study 4 groups included in the HEIRS Study Comprehensive Clinical Exam which will allow us to examine both the impact of hemochromatosis genotype and phenotypic expression of iron overload. The first group will be individuals who are HFE gene positive and are phenotype positive for elevated iron (elevated serum ferritin (SF) and elevated transferring saturation (TS)). The second group will be individuals who are HFE gene negative and are phenotype positive. The third group will be individuals who are HFE gene positive and are phenotype negative for elevated iron. The final group will be individuals who are HFE gene negative and are phenotype negative for elevated iron. The total number of subjects to be studied will be 1,157. Although there is an increased risk of development of a variety of clinical conditions in patients with HH, it is not known whether HH is associated with leukocyte telomere length and whether certain treatment and lifestyle activities can buffer the relationship. This study is innovative in that the cumulative stress and heritable predispositions for disease are represented in telomere length. This study will extend previous knowledge of accelerated aging and morbidity among individuals with hemochromatosis and iron overload by examining factors that may accelerate or slow the biological aging process and corresponding development of disease. This project has potential implications for early detection and screening using phenotypic markers as well as compliance with treatment and a healthy lifestyle.